Certain research related to the subject matter of the present application was conducted under monetary grants from the United States of America and a paid up, nonexclusive, irrevocable and non-transferrable license is hereby granted to the United States of America for governmental purposes.
The present invention relates to imaging, detection or treatment of tissue with labeled steroids and, in particular, to imaging of a living internal tissue by treatment of the tissue with a 16-.sup.123 I-estradiol.
Medical science has often found the use of non-invasive techniques to study various tissues within a body to be very helpful in diagnosis of various diseases or injuries. For this purpose, various detectable materials have been developed over the years which are designed to be applied to living tissue to be studied, so as to provide an image of the tissue outside of the body. Preferably, such materials bind with the particular tissue to be studied. It has also been found that such imaging materials often help in studying tissues outside of a body, as for example in assays in which an amount of binding site present is measured. Thus, the detectable materials are often usable for both in vivo and in vitro studies.
Various detectable materials are imageable or detectable in different ways. For example, some materials that have been suggested for imaging or assay purposes release radiation which can be detected. Other materials are suitable for detection by nuclear magnetic resonance (NMR) devices or the like.
One of the major limitations on materials used for detection within living animals is that the material should be relatively benign to the animal host. Therefore, although high concentrations of strongly radioactive materials may often provide a good imaging source, they are not generally compatible with use in living tissue. In addition, where a carrier mechanism is utilized to preferentially carry the detectable material to a particular tissue of interest, certain labels may render the carrier generally ineffective in preferentially binding to that particular tissue or the receptors therein to be studied.
Steroids have been heavily studied for use as carriers for detectable materials. One particularly effective group of steroids has been estrogen and its derivatives, which seek out organs in the body having estrogen receptors, including such organs as the ovaries, cervix, uterus, breast, and brain. Suitable estrogen receptors are also sometimes present in some types of cancerous lung tissue, as well as skin, bones, and testes.
Various halogens have often been suggested as effective detectable agents, since the halogens often are readily combinable with estrogen. While certain combinations of estrogens and halides may affect the binding ability of an estrogen carrier, certain other combinations do not substantially modify the binding ability of the estrogen with estrogen receptors. One particular type of halogen that has been proposed as a label is radioactive iodine. For example, Hochberg has developed a process to make estrogens labled with iodine 125.
Problems have arisen, however, with the use of iodine, even though the affect of iodine and iodinated steroids in animals has been heavily studied. One of the major problems associated with the use of certain common radioactive isotopes of iodine has been that they often do not have sufficient energy associated with their radioactive decay to substantially penetrate the animal body, when used in vivo, and consequently do not provide clear images on a detector. In addition, the readily available radioactive isotope .sup.125 I has a fairly long half-life and it is generally not desirable to place long half-life radioisotopes within an animal body, since damage from radioactivity is more likely to occur with the longer lived isotopes. Also, a greater amount of the radioactive iodine may need to be injected when the half-life is long, in order to provide enough decay to be readily detectable.
Iodine isotope I-123 substantially overcomes the problem with the long half-life, since it has a half-life of only approximately 13.3 hours; and, further has a fairly high energy gamma radiation decay, generally making it readily detectable. In addition, it is found that images produced by .sup.123 I decay are generally sharp or clear. Unfortunately, the short half-life of .sup.123 I has effectively prevented previous use of .sup.123 I-iodinated estradiols, since conventional methods of producing them have typically taken between 20 to 40 hours, conventional methods of synthesis generally produce mixtures, and conventional syntheses have generally led to relatively low yields. Thus, by the end of the production of the .sup.123 I-iodonated estradiol, a substantial number of half-lives may have already run; and, especially if the yield is relatively low, the iodinated product may not be generally readily utilizable for imaging or assays.
Estradiol iodonated with iodine-123 is now manufacturable within a two to four hour time period and will be available from Biomedical Research Labs of Lenexa, Kan., the assignee of the present application, or through its licensees. A synthesis for the production of estradiol iodinated with iodine-123 suitable for use with the methods of the present invention is disclosed in U.S. Pat. No. 4,659,517 which is incorporated herein by reference. The present application is indirectly a continuation-in-part of this issued patent.
With general availability of the estradiol effectively iodonated with the I-123 isotope, there has been a desire to produce imaging methods for utilization of the I-123 compound.